This project is intended to elucidate the conditions contributing to myocardial injury in chronic alcoholism. Studies in animal models will supplement the human studies to control some of the variables not amenable to regulation in man. Duration of alcoholism as well as its intensity, in terms of frequency and quantity of intake, are viewed as critical importance in determining clinical evidence of heart disease. Factors which may potentiate the effects of ethanol by alteration of interstitial collagen or cardiac cell lipid metabolism also require elucidation. These include associated tobacco use, dietary conditions, intake of congeners of ethanol, age and sex. In addition the daily dose of ethanol which may be considered as the minimal toxic dose on a chronic basis needs to be defined. Postmortem study of the human myocardium will enable a correlation of altered composition and clinical course. The potential for reversibility of the cardiac lesions is not clearly understood and will be assessed under control conditions. Studies in man will involve long term follow-up of patients with a preclinical cardiac abnormality, or cardiomyopathy, in the alcoholism clinic using noninvasive tests of cardiac function. Of particular interest will be the course of the disease in those who present as myocardial infarction without evidence of coronary obstructive disease. Clinical studies have suggested an increased risk of sudden death in alcoholics without cardiomegaly, presumably due to ventricular fibrillation. In the chronic animal model, which exhibits conduction abnormalities in response to chronic ethanol use, the susceptibility to this arrhythmia will be evaluated. To evaluate this problem in man, patients admitted with acute intoxication will be monitored for arrhythmias and the conditions associated with their genesis.